Department of Urology, Peking University First Hospital, Beijing, 100034, China.
Key Laboratory of Genomic and Precision Medicine, Beijing Institute of Genomics, Chinese Academy of Sciences, Beijing, 100101, China.
Clin Epigenetics. 2018 Jul 13;10(1):94. doi: 10.1186/s13148-018-0527-7.
5-Hydroxymethylcytosine (5hmC) is converted from 5-methylcytosine (5mC) by a group of enzymes termed ten-eleven translocation (TET) family dioxygenases. The loss of 5hmC has been identified as a hallmark of most types of cancer and is related to tumorigenesis and progression. However, the role of 5hmC in bladder cancer is seldom investigated. Vitamin C was recently reported to induce the generation of 5hmC by acting as a cofactor for TET dioxygenases. In this study, we explored the role of 5hmC in bladder cancer and the therapeutic efficacy of vitamin C in increasing the 5hmC pattern.
5hmC was decreased in bladder cancer samples and was related to patient overall survival. Genome-wide mapping of 5hmC in tumor tissues and vitamin C-treated bladder cancer cells revealed that 5hmC loss was enriched in cancer-related genes and that vitamin C treatment increased 5hmC levels correspondingly. Vitamin C treatment shifted the transcriptome and inhibited the malignant phenotypes associated with bladder cancer cells in both in vitro cell lines and in vivo xenografts.
This study provided mechanistic insights regarding the 5hmC loss in bladder cancer and a rationale for exploring the therapeutic use of vitamin C as a potential epigenetic treatment for bladder cancer.
5-羟甲基胞嘧啶（5hmC）可由一组被称为 ten-eleven translocation（TET）家族双加氧酶的酶从 5-甲基胞嘧啶（5mC）转化而来。5hmC 的缺失已被确定为大多数类型癌症的标志，与肿瘤发生和进展有关。然而，5hmC 在膀胱癌中的作用很少被研究。最近有报道称，维生素 C 可作为 TET 双加氧酶的辅助因子诱导 5hmC 的产生。在这项研究中，我们探讨了 5hmC 在膀胱癌中的作用以及维生素 C 增加 5hmC 模式的治疗效果。
膀胱癌样本中 5hmC 减少，与患者总生存相关。对肿瘤组织和维生素 C 处理的膀胱癌细胞中的 5hmC 进行全基因组作图显示，5hmC 缺失在癌症相关基因中富集，而维生素 C 处理相应地增加了 5hmC 水平。维生素 C 处理改变了转录组，并抑制了体外细胞系和体内异种移植中与膀胱癌相关的恶性表型。
这项研究为膀胱癌中 5hmC 的缺失提供了机制上的见解，并为探索维生素 C 作为膀胱癌潜在的表观遗传治疗的治疗用途提供了依据。
